Biology subjects

Itokazu, T.

Publications and source records attributed to Itokazu, T..

3 recordsLinked to original sources

bioRxiv2026

Sensory neuron dysfunction and hyperexcitability in dorsal root ganglia at disease onset in the SOD1G93A mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder traditionally characterized by motor neuron degeneration, but emerging evidence indicates sensory system involvement. Despite reports of sensory abnormalities in some patients, the molecular and functional alterations in dorsal root ganglion (DRG) neurons remain insufficiently characterized. We investigated DRG pathology at disease onset in 12-week-old SOD1G93A mice using an integrated transcriptomic, morphological, and electrophysiological approach. RNA sequencing of lumbar DRG identified 35 differentially expressed genes, predominantly upregulated, enriched in oxidative stress-related and phagosome pathways. Comparative analysis with motor neuron transcriptomes revealed distinct gene expression profiles, indicating sensory neuron-specific molecular responses. Immunohistochemistry demonstrated reduced soma diameter in both A- and C-fiber DRG neurons. Nav channel colocalization increased for Nav1.7 in A fibers and Nav1.8 in both fiber types, whereas Nav1.6 was unchanged. Whole-cell patch-clamp recordings showed depolarized resting membrane potential, increased spike amplitude, and enhanced repetitive firing in A-fiber neurons, consistent with hyperexcitability, while C fibers showed no significant functional changes. These findings demonstrate early molecular, structural, and functional alterations in primary sensory neurons in ALS, supporting pathology beyond motor neurons and identifying sensory neuron excitability as a potential therapeutic target.

neuroscience↗

bioRxiv2025

Intermingled representation of oral cavity in mouse trigeminal ganglion

Somatotopy serves as a fundamental principle underlying sensory information processing, traditionally emphasized in the study of the cerebral cortex. However, little effort has been directed towards unraveling the spatial organization characterizing the earlier stages of sensory pathways. In this study, we developed a novel methodology to visualize individual neurons within the trigeminal ganglion--a crucial cluster of cell bodies of sensory neurons innervating the face. Our investigations revealed a reliable sensory response to stimulation of the lower teeth or lip within this ganglion. The responsive neurons were confined to a specific portion of the trigeminal ganglion, consistent with innervation of the lower oral cavity by the mandibular nerve. Contrary to our expectations, we did not observe a discernible map delineating specific regions of the oral cavity. Instead, the spatial representation of the teeth and lips exhibited unexpected intermingling. These findings challenge conventional understandings rooted in cortical maps and suggest that such conceptual frameworks may not be applicable to earlier stages of sensory pathways for the oral cavity. Our study sheds light on the complex spatial organization of sensory processing in the trigeminal system, highlighting the need for further research to elucidate the underlying mechanisms and implications for sensory perception and clinical interventions. Impact statementIn vivo calcium imaging revealed that neurons responding to tooth stimulation are sparsely distributed in the trigeminal ganglion, intermixed with neurons responding to lip stimulation.

neuroscience↗

bioRxiv2023

Enhanced Aversive Signals During Classical Conditioning in Dopamine Axons in Medial Prefrontal Cortex

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse activity in dopamine axons responsive to both reward and aversive stimuli. Some axons exhibited a preference for reward, while others favored aversive stimuli, and there was a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings indicate that a group of mesocortical dopamine axons encodes aversive-related signals, which are modulated by both classical conditioning across days and trial-by-trial discrimination within a day. Impact statementTwo-photon calcium imaging revealed that many mesocortical dopamine axons show enhanced selectivity for aversive cue processing during classical conditioning.

neuroscience↗